PDF(Pubmed)
Abstract：
BACKGROUND: Malformations of cortical development (MCD) are a group of congenital disorders characterized by structural abnormalities in the brain cortex. The clinical manifestations include refractory epilepsy, mental retardation, and cognitive impairment. Genetic factors play a key role in the etiology of MCD. Currently, there is no curative treatment for MCD. Phenotypes such as epilepsy and cerebral palsy cannot be observed in the fetus. Therefore, the diagnosis of MCD is typically based on fetal brain magnetic resonance imaging (MRI), ultrasound, or genetic testing. The recent advances in neuroimaging have enabled the in-utero diagnosis of MCD using fetal ultrasound or MRI.
METHODS: The present study retrospectively reviewed 32 cases of fetal MCD diagnosed by ultrasound or MRI. Then, the chromosome karyotype analysis, single nucleotide polymorphism array or copy number variation sequencing, and whole-exome sequencing (WES) findings were presented.
RESULTS: Pathogenic copy number variants (CNVs) or single-nucleotide variants (SNVs) were detected in 22 fetuses (three pathogenic CNVs [9.4%, 3/32] and 19 SNVs [59.4%, 19/32]), corresponding to a total detection rate of 68.8% (22/32).
CONCLUSIONS: The results suggest that genetic testing, especially WES, should be performed for fetal MCD, in order to evaluate the outcomes and prognosis, and predict the risk of recurrence in future pregnancies.
METHODS: The present study retrospectively reviewed 32 cases of fetal MCD diagnosed by ultrasound or MRI. Then, the chromosome karyotype analysis, single nucleotide polymorphism array or copy number variation sequencing, and whole-exome sequencing (WES) findings were presented.
RESULTS: Pathogenic copy number variants (CNVs) or single-nucleotide variants (SNVs) were detected in 22 fetuses (three pathogenic CNVs [9.4%, 3/32] and 19 SNVs [59.4%, 19/32]), corresponding to a total detection rate of 68.8% (22/32).
CONCLUSIONS: The results suggest that genetic testing, especially WES, should be performed for fetal MCD, in order to evaluate the outcomes and prognosis, and predict the risk of recurrence in future pregnancies.
摘要：
背景：皮质发育畸形（MCD）是一组以大脑皮质结构异常为特征的先天性疾病。临床表现包括难治性癫痫,智力迟钝,和认知障碍。遗传因素在MCD的病因中起着关键作用。目前,MCD没有治愈性治疗。在胎儿中无法观察到诸如癫痫和脑瘫之类的表型。因此,MCD的诊断通常基于胎儿脑磁共振成像（MRI），超声，或者基因检测.神经影像学的最新进展使使用胎儿超声或MRI在子宫内诊断MCD成为可能。
方法：本研究回顾性分析32例经超声或MRI诊断的胎儿MCD。然后，染色体核型分析，单核苷酸多态性阵列或拷贝数变异测序，和全外显子组测序（WES）的发现。
结果：在22个胎儿中检测到致病性拷贝数变异（CNVs）或单核苷酸变异（SNVs）（三个致病性CNVs[9.4％，3/32]和19SNV[59.4%，19/32])，总检出率为68.8%(22/32)。
结论：结果表明，基因检测，尤其是WES,应该对胎儿MCD进行检查，为了评估结果和预后，并预测未来怀孕的复发风险。
方法：本研究回顾性分析32例经超声或MRI诊断的胎儿MCD。然后，染色体核型分析，单核苷酸多态性阵列或拷贝数变异测序，和全外显子组测序（WES）的发现。
结果：在22个胎儿中检测到致病性拷贝数变异（CNVs）或单核苷酸变异（SNVs）（三个致病性CNVs[9.4％，3/32]和19SNV[59.4%，19/32])，总检出率为68.8%(22/32)。
结论：结果表明，基因检测，尤其是WES,应该对胎儿MCD进行检查，为了评估结果和预后，并预测未来怀孕的复发风险。
